First pass effect

[1][2] The effect is most associated with orally administered medications, but some drugs still undergo first-pass metabolism even when delivered via an alternate route (e.g., IV, IM, etc.).

The liver is the major site of first pass effect; however, it can also occur in the lungs, vasculature or other metabolically active tissues in the body.

Notable drugs that experience a significant first pass effect are buprenorphine, chlorpromazine, cimetidine, diazepam, ethanol (drinking alcohol), imipramine, insulin, lidocaine, midazolam, morphine, pethidine, propranolol, and tetrahydrocannabinol (THC).

[ambiguous] Physiologically based pharmacokinetic models (PBPK) are used to predict first-pass metabolism, although they require compound-specific adjustments due to variability in intestinal mucosal permeability and other factors.

[16] In vitro models, such as the use of microfluidic chips that simulate the gut and liver, allow first-pass metabolism to be studied more accurately, facilitating the development of drugs with better absorption profiles.